fig6a: Effects of C-K on the differentiation of CD3+CD4+ T lymphocytes in CIA mice. The population size of different T lymphocyte subsets was determined by flow cytometry. The percentages of the T lymphocyte subsets were analyzed by gating on lymphocytes. The number in each plots represents the expression of that subset of T cells among lymphocytes. Mean±SD. n=10. bP<0.05 vs normal mice.

Mentions:
The subgroups of T lymphocytes were examined by flow cytometry. The results showed that the percentages of CD3+CD4+ cells (analogous to helper T cells, Th cells), CD4+CD154+ cells (Th cells expressing co-stimulatory molecules CD154), CD4+CD69+ cells (analogous to activated T cells) and CD4+CD62L−CD44hi cells (analogous to effector memory T cells, TEM) in the spleens of CIA mice were significantly higher compared with those in normal mice, whereas the percentages of CD4+CD62L+CD44low cells (analogous to naive cells) and CD4+CD25+ Foxp3+ cells (analogous to regulatory T cells, Tregs) were significantly lower. C-K treatment decreased the proportions of CD4+CD154+, CD4+CD69+, and CD4+CD62L−CD44hi cells (Figures 6B, 6C, and 6D) and increased the percentages of CD4+CD62L+CD44low and CD4+CD25+ Foxp3+ cells (Figures 6B and 6F). The proportion of CD3+CD4+Th cells was not affected by C-K or MTX administration (Figure 6A). The data we obtained indicated that C-K substantially modulated the activation and differentiation of T lymphocytes in CIA mice, which might be a novel mechanism underlying the effects of C-K in the treatment of RA.

fig6a: Effects of C-K on the differentiation of CD3+CD4+ T lymphocytes in CIA mice. The population size of different T lymphocyte subsets was determined by flow cytometry. The percentages of the T lymphocyte subsets were analyzed by gating on lymphocytes. The number in each plots represents the expression of that subset of T cells among lymphocytes. Mean±SD. n=10. bP<0.05 vs normal mice.

Mentions:
The subgroups of T lymphocytes were examined by flow cytometry. The results showed that the percentages of CD3+CD4+ cells (analogous to helper T cells, Th cells), CD4+CD154+ cells (Th cells expressing co-stimulatory molecules CD154), CD4+CD69+ cells (analogous to activated T cells) and CD4+CD62L−CD44hi cells (analogous to effector memory T cells, TEM) in the spleens of CIA mice were significantly higher compared with those in normal mice, whereas the percentages of CD4+CD62L+CD44low cells (analogous to naive cells) and CD4+CD25+ Foxp3+ cells (analogous to regulatory T cells, Tregs) were significantly lower. C-K treatment decreased the proportions of CD4+CD154+, CD4+CD69+, and CD4+CD62L−CD44hi cells (Figures 6B, 6C, and 6D) and increased the percentages of CD4+CD62L+CD44low and CD4+CD25+ Foxp3+ cells (Figures 6B and 6F). The proportion of CD3+CD4+Th cells was not affected by C-K or MTX administration (Figure 6A). The data we obtained indicated that C-K substantially modulated the activation and differentiation of T lymphocytes in CIA mice, which might be a novel mechanism underlying the effects of C-K in the treatment of RA.

Bottom Line:
C-K treatment significantly suppressed TNF-α and anti-CII antibody levels, and increased IFN-γ level in the joints of CIA mice, but did not alter IL-4 production.Methotrexate treatment exerted comparable effects in all these experiments.C-K suppresses the progression of CIA through regulating TCR, CD28, CTLA-4 and PD-1 expression, thus inhibiting the abnormal activation and differentiation of T lymphocytes.